Abscopal effect of focused ultrasound combined immunotherapy in animal solid tumor model: a systematic reviews and meta-analysis

Abstract

Introduction: The abscopal effect, a systemic anti-tumor response triggered by localized treatment, has gained attention but remains poorly understood. This study evaluates the efficacy and consistency of focused ultrasound (FUS) combined with immunotherapy in inducing the abscopal effect.

Methods: A systematic review and meta-analysis were conducted on preclinical studies using solid tumor models. Data on tumor response, immune modulation, and survival outcomes were analyzed to assess the combination therapy's effectiveness.

Results: FUS combined with immunotherapy enhanced anti-tumor responses at local and distant sites, with evidence of immune activation and increased abscopal effect rates. However, heterogeneity across tumor models and protocols was observed.

Discussion: The findings provide a theoretical basis for FUS-immunotherapy combinations in cancer treatment, while emphasizing the need for standardized protocols and further research to elucidate underlying mechanisms.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023460710.

Keywords: abscopal effect; focused ultrasound; immunotherapy; meta-analysis; systematic review.

Figure 1

Flowchart of the study selection process. A systematic search was conducted using English databases (Medline, Embase, Web of Science) and Chinese databases (SinoMed, CNKI, and Wanfang), covering the period from January 1, 2001, to October 14, 2024.

Figure 2

Study quality assessed using SYRCLE’s animal study bias tool. The quality assessment checklist comprises six components: (1) selection bias (sequence generation, baseline characteristics, and allocation concealment); (2) performance bias (randomization and blinding); (3) detection bias (randomized outcome assessment and blinding of outcome assessors); (4) attrition bias (incomplete outcome data); (5) reporting bias (selective outcome reporting); and (6) other biases (model evaluation, temperature control, pharmaceutical manufacturing institutions, conflicts of interest, etc.).

Figure 3

Forest plots and funnel plots of the main outcome. On the left side of the forest plot, the combined group (focused ultrasound therapy + immunotherapy) demonstrated greater benefit, while the right side indicated superior outcomes for the immunotherapy-only group. (A) Forest plots for distant tumor volume summarize the effect size of the standard mean difference, favoring the combined group, with the confidence intervals not crossing zero. (B) Funnel plots of distant tumor volume. (C) Forest plots for survival time summarize hazard ratios (HR), with values on the left side, indicating a benefit from the combined group, and confidence intervals not crossing one. (D) Funnel plots of survival time. (E) Forest plots for treated tumor volume summarize the effect size of the standard mean difference, favoring the combined group, with confidence intervals not crossing zero. (F) Funnel plots of treated tumor volume. The summary effect size is represented by ◆ (focused ultrasound therapy: UA).

Figure 4

Impact on Immune microenvironment of focused ultrasound combined with immunotherapy in the spleen, serum, therapeutic draining lymph nodes, treated tumors, and distant tumors.